One year treatment with haloperidol or clozapine fails to alter neostriatal D1- and D2-dopamine receptor sensitivity in the rat.

Rats were treated continuously with either haloperidol (HAL), clozapine (CLOZ) or tap water for one year. There were no differences between age-matched control and antipsychotic drug (APD) treated groups regarding the effects of the D1-agonist (+)-SKF 38393 or the D2-agonist quinpirole on striatal cAMP content. However, the combination of SKF (10 microM) and quinpirole (1 microM) produced a marked synergistic response in HAL-treated animals as compared to controls. Our data fail to support the hypothesis that APD produce their neurological side effects by inducing D2-receptor hypersensitivity in the basal ganglia. However, the results do suggest that chronic APD treatment alters the interaction between D1- and D2-neostriatal receptors.